title: Circadian regulation of melatonin in the retina of Xenopus laevis: limitation by serotonin availability.
abstract: Treatments expected to increase retinal serotonin levels were found to stimulate melatonin production by cultured eyecups from Xenopus laevis. The monoamine oxidase inhibitor pargyline (100 microM) caused a sixfold increase in melatonin release, and the serotonin precursor 5-hydroxy-L-tryptophan (100 microM) caused a 70-fold increase. Both acted synergistically with eserine, an inhibitor of melatonin deacetylation in the retina. The effect of 5-hydroxytryptophan was dose dependent, with effects increasing from 1 to 100 microM. Increasing the tryptophan level in the culture medium had no effect on melatonin release. These results indicate that the rate-limiting step in retinal melatonin synthesis is 5-hydroxylation of tryptophan. Melatonin released from individual eyecups in superfusion culture in constant darkness with and without added 5-hydroxy-L-tryptophan was monitored over a 5-day period. Control eyecups released low levels of melatonin, with circadian rhythmicity persisting for 1-3 days. With 5-hydroxy-L-tryptophan added, melatonin levels were elevated 10-20-fold at all times, and rhythmicity was apparent for as long as five cycles. This provides a model system for studies of the circadian clock in the eye.
authors.affiliation: Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: G M
authors.initials: GM
authors.lastname: Cahill
authors.forename: J C
authors.initials: JC
authors.lastname: Besharse
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001682:Biological Availability; D002940:Circadian Rhythm; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D008550:Melatonin / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D011863:Radioimmunoassay; D012160:Retina / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014982:Xenopus laevis / Q000378:metabolism*
chemical_list: D012701:Serotonin; D010293:Pargyline; D006916:5-Hydroxytryptophan; D014365:Tryptophan Hydroxylase; D008550:Melatonin